Desymmetrization of Diboron(4) by a Trifluorination B-Masking Strategy: Practical Synthesis of Unsymmetrical Diboron Species

Herein, we report a straightforward practical and simple method for efficiently synthesizing a BF3-containing unsymmetrical diboron salt. This method involves the direct desymmetrization of commercially available diboron(4). This desymmetrization is based on a selective B-masking strategy via nucleophilic trifluorination, providing the elusive diborons bearing a trifluoroborate group. The synthetic utility of these salts is demonstrated through various examples of (sequential) B-ligand interconversions, enabling the synthesis of unsymmetrical diboron derivatives. These products, which serve as valuable building blocks, are obtained in gram-scale and high yields.


Materials and General Remarks.
Unless otherwise stated, reactions were performed in oven-dried glassware fitted with rubber septa under inert atmosphere (N2) and were stirred with teflon-coated magnetic stirring bars.Materials and chemicals were purchased from Sigma-Aldrich Inc., Combi-Blocks Inc., Alfa Aesar., and other commercial suppliers.Liquid reagents and solvents were transferred via syringe using standard Schlenk techniques.Solvents DMSO, hexane, methanol and acetonitrile were used as commercial grade and used as received with no further drying.Tetrahydrofuran (THF), diethyl ether (Et2O), and dichloromethane (CH2Cl2) were used from a solvent purification system.All other reagents were used as received unless otherwise noted.Thin layer chromatography (TLC) was performed using silica gel 60 F-254 pre-coated plates (0.25 mm) and visualized by UV irradiation ƛ=232 nm, CAM stain, KMnO4 stain, and other stains.Silica gel of particle size 230-400 mesh was used for flash chromatography, Flash chromatography (FC) was performed using CombiFlash, with SiO2 columns. 1 H-NMR and 13 C-NMR spectra were recorded on 400, 500 MHz spectrometers with 13 C-NMR operating frequencies of 101, 126 MHz, 11 B-NMR operating frequencies of 128, 160 MHz, 19 F-NMR operating frequencies of 376, 471 MHz respectively. 1H-NMR and 13 C-NMR spectra were referenced to TMS as an internal standard with a deuterated solvent unless otherwise stated.X-Ray structure was visualized with PLATON 1 .Chemical shifts (δ) are reported in ppm relative to the residual solvents (CDCl3) signal (δ = 7.26 for 1 H-NMR and δ = 77.16for 13 C-NMR) and (DMSO-d6) signal (δ = 2.50 (ppm) for 1 H-NMR and δ = 39.5 (septet) for 13 C-NMR).Data for 1 H-NMR spectra are reported as follows: chemical shift (multiplicity, coupling constants, and number of hydrogen).Abbreviations are as follows: s (singlet), d (doublet), t (triplet), q (quartet), p (pentate), m (multiplet), brs (broad singlet).High-Resolution Mass Spectrometry (HRMS) were recorded on a SCIEX, X500R Q-TOF-MS (Quadrupole-TOF) using acetonitrile or methanol as solvent in a direct injection.Melting points (m.p) were determined with Stuart Scientific SMP 10 melting point apparatus.
Pinacol-d12 [2,3-bis(methyl-d3)butane-1,1,1,4,4,4-d6-2,3-diol] was prepared in accordance to previous reported procedure. 2der nitrogen (N2) atmosphere, magnesium (1 g, 68 mmol) was added into a three necked, flame dried round bottom flask, 20 mL of dry benzene was then added into the same flask and the mixture was stirred for 5 minutes at room temperature.Then a solution of mercury (II) chloride (1.84 g, 6.8 mmol) in acetone-d6 (S-1) (68 mmol, 5 mL) was added dropwise through a dropping funnel and kept stirring until the vigorous reaction was complete.Then another 5 mL of acetone-d6 (S-1) with benzene (10 mL) was added and reaction was refluxed using an oil bath for 3 hours.While hot, water (2.5 mL) was added carefully to the reaction mixture and the mixture was stirred for additional 1 hour at reflux.After that, the mixture was filtered while hot, the solids were returned to the flask and refluxed using an oil bath for 5 minutes with a fresh benzene (10 mL), and filtered again while hot.The filtrates were then combined, and reduced to one half of its volume using a rotary evaporator.Then water (5 mL) was added dropwise to the remaining clear solution of benzene while cold, resulting in the precipitation of pinacol-d12 hydrate as a white solid that was further washed with benzene.Pinacol-d12 hydrate was hydrated by heating the solids at 150 C ° using an oil bath for 3 hours and then distilled to give 3.5 g (40 % yield) of the desired pinacol-d12 as a yellowish gummy solid.The spectral data are consistent with those reported in the literature.2

Procedure-A and Characterizations for Trifluorodiboron salt Products (11).
Procedure-A: The reaction took place in an open air environment.Diborone (10) (1 mmol, 1 equiv, 254 mg) was dissolved in a mixture of acetonitrile (5 mL) and methanol (5 mL) in an open flask.
To this mixture, a solution of a fluoride salt [4 mmol, 4 equiv, either KF (232.3 mg in 0.5 mL H2O) or CsF (604 mg in 0.5 mL H2O)] was added, and the resulting mixture was stirred at room temperature for 1 minute.Then, L-tartaric acid (2.05 mmol, 2.05 equiv, 307 mg in 3 mL THF) was added dropwise to the rapidly stirred turbid solution.During this addition, a white precipitate formed.The reaction mixture was filtered to remove the white precipitate and washed thoroughly with excess acetonitrile (10 mL).The filtrate was then concentrated in a rotary evaporator to obtain a crude solid.Subsequent washing with diethyl ether and hexane yielded the corresponding trifluoroborate (11) as a white solid, which was further dried under high vacuum overnight.

X-ray structure of 11a CCDC : 2329696
The ellipsoid contour is with 50% probability level.
The organic layers were combined and washed with brine, dried over MgSO4, and concentrated under reduced pressure using evaporator to obtain a crude material.The crude material was further purified by a short column on silica gel, resulting in the formation of product (12).
To the above mixture, a solution of CsF (4 mmol, 600 mg, in H2O 0.2 mL) was added, and the mixture was stirred at room temperature for 1 minutes.Next L-tartaric acid (2.04 mmol, 306 mg, in 4 mL THF) was added dropwise to the rapidly stirred solution, during that time a white precipitate crashed out.After 8 minutes, the reaction mixture was filtered to remove the white precipitate and washed thoroughly with excess of acetonitrile (8 mL), then the filtrate was concentrated in a rotary evaporator to give a crude solid.Then washing with diethyl ether and hexane, furnished the corresponding Bdan-BF3Cs (13a) as a white solid via filtration.

Figure S1 :
Figure S1: Reaction setup for the preparation of product 11a.

Figure S2 :
Figure S2: A picture of product 11a from a large-scale synthesis.

Figure S6 .
Figure S6.Pictures of product 12b from a large-scale synthesis.

Note:
Product Bdan-BF3Cs (13a) can be used immediately after isolation for the next step Figure S8 or kept under Nitrogen atmosphere while protected from light, otherwise compound starts to decompose while changing color to purple Figure S9.To remove trace amounts of solvents (Et2O and Hexane) the salt was left to dry in a Nitrogen (N2) filled Glovebox, while protected from light.

Figure S8 .
Figure S8.Picture of product 13a immediately after filtration.

Figure S9 .
Figure S9.Picture of product 13a after exposing to light and moisture.

Figure S10 .
Figure S10.Pictures of product 14b from a large-scale synthesis.

Table S1 .
Optimization table for trifluoroborate salts (11a) preparation: a Reactions were carried out with 0.20 mmol of 10a and 0.8 mmol of MF along with 2 mL of Solvent-1, 2 mL of Solvent-2, 0.7 mL of Solvent-3 and 0.41mmol of AMS (Alkali Metal Sponge) in an open flask at rt for the indicated amount of time.b Isolated yield.c full conversion (FC) by 1 H-NMR.